# Comparative effectiveness of combination therapy with SGLT‐2 inhibitors and GLP‐1 RAs compared with SGLT‐2 inhibitors in individuals with type 2 diabetes: A prevalent new‐user cohort study

## TL;DR

Combining SGLT-2 inhibitors and GLP-1 RAs in type 2 diabetes patients may reduce all-cause mortality and heart-related risks compared to using SGLT-2 inhibitors alone.

## Contribution

This study provides real-world evidence on the comparative effectiveness of combined SGLT-2 inhibitor and GLP-1 RA therapy in type 2 diabetes.

## Key findings

- Combination therapy was linked to a 29% lower risk of all-cause mortality.
- Reduced hazards were also observed for cardiovascular events and heart failure.
- Benefits were consistent across subgroups and sensitivity analyses.

## Abstract

To evaluate the effectiveness of combination therapy with sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) compared with continued SGLT‐2 inhibitor therapy in routine practice among individuals with type 2 diabetes.

We used nationwide BARMER health claims data and implemented a prevalent new‐user design. Individuals initiating a GLP‐1 RA, either simultaneously with SGLT‐2 inhibitors or during ongoing SGLT‐2 inhibitor exposure, were matched to SGLT‐2 inhibitor continuers using hybrid exposure sets and time‐conditional propensity scores. The study cohort included individuals enrolled between 2013 and 2023, with possible follow‐up including 2024. The primary outcome was all‐cause mortality. Secondary outcomes included a modified cardiovascular composite (all‐cause mortality, myocardial infarction, stroke), heart failure, nephropathy, and renal failure. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

Among 21 664 matched pairs with a median follow‐up of 1.3 years, combination therapy was associated with a 29% lower hazard of all‐cause mortality (HR 0.71, 95% CI 0.63–0.80), consistent across subgroups and sensitivity analyses. Hazard reductions were also observed for the modified cardiovascular composite (HR 0.81, 95% CI 0.74–0.88) and heart failure (HR 0.78, 95% CI 0.68–0.89).

In this large real‐world cohort, combination therapy with SGLT‐2 inhibitors and GLP‐1 RAs was associated with a lower hazard of all‐cause mortality, while most secondary cardiorenal outcomes showed generally favourable but imprecise estimates. These findings suggest that sustained concurrent use of both drug classes may offer meaningful clinical benefits in routine practice, although residual confounding cannot be fully excluded.